The effectiveness of clopidogrel in the prevention of thrombotic complications in patients with acute coronary syndrome and genetic factors

This review article presents the current views on genotyping during administration of clopidogrel - an antiplatelet drug from the class of thienopyridines, for patients with acute coronary syndrome. Highlighted were the data on genetic disorders affecting the absorption and metabolism of clopidogrel. The gene ABCB1 (MDR1) encodes the intestinal transporter P-glycoprotein. The variability of this gene may affect the bioavailability of clopidogrel. However, data on the relationship between C3435T polymorphism of ABCB1 gene and the expression of P-glycoprotein still remain controversial. Differences in the effects of C3435T may reflect the differences in the frequency of ABCB1 polymorphism among ethnic groups and the complex of effects of different polymorphisms in the same gene within a haplotype, or confounding factors of the environment. The most important role in the metabolism of clopidogrel is played by cytochrome P-450 (iso-enzyme CYP2C19). Several large studies have confirmed the prognostic significance of CYP2C19 polymorphism in patients receiving clopidogrel. In a recent meta-analysis of nine pharmacogenetic studies of clopidogrel, which included 9685 patients with acute coronary syndrome, revealed was a significant association between the homozygous and heterozygous alleles with reduced CYP2C19 function and an increased risk of death due to cardiovascular disease, myocardial infarction or stroke. Two large randomized studies of CYP2C19 genotyping did not reveal any relationship between its variants and the occurrence of cardiovascular events in patients with acute coronary syndrome or atrial fibrillation. Thus, in genetic studies of the antiplatelet effectiveness of clopidogrel, there are many uncertainties; domestic data on this subject is extremely scarce.